Immunomodulatory effects of cyclophosphamide and implementations for vaccine design.

Antonella Sistigu, Sophie Viaud, Nathalie Chaput, Laura Bracci, Enrico Proietti, Laurence Zitvogel

Research output: Contribution to journalArticle

Abstract

Drug repositioning refers to the utilization of a known compound in a novel indication underscoring a new mode of action that predicts innovative therapeutic options. Since 1959, alkylating agents, such as the lead compound cyclophosphamide (CTX), have always been conceived, at high dosages, as potent cytotoxic and lymphoablative drugs, indispensable for dose intensity and immunosuppressive regimen in the oncological and internal medicine armamentarium. However, more recent work highlighted the immunostimulatory and/or antiangiogenic effects of low dosing CTX (also called "metronomic CTX") opening up novel indications in the field of cancer immunotherapy. CTX markedly influences dendritic cell homeostasis and promotes IFN type I secretion, contributing to the induction of antitumor cytotoxic T lymphocytes and/or the proliferation of adoptively transferred T cells, to the polarization of CD4(+) T cells into TH1 and/or TH17 lymphocytes eventually affecting the Treg/Teffector ratio in favor of tumor regression. Moreover, CTX has intrinsic "pro-immunogenic" activities on tumor cells, inducing the hallmarks of immunogenic cell death on a variety of tumor types. Fifty years after its Food and Drug Administration approval, CTX remains a safe and affordable compound endowed with multifaceted properties and plethora of clinical indications. Here we review its immunomodulatory effects and advocate why low dosing CTX could be successfully combined to new-generation cancer vaccines.

Original languageEnglish
Pages (from-to)369-383
Number of pages15
JournalSeminars in Immunopathology
Volume33
Issue number4
Publication statusPublished - Jul 2011

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Cyclophosphamide
Vaccines
Neoplasms
Drug Repositioning
T-Lymphocytes
Drug Approval
Cancer Vaccines
Alkylating Agents
Cytotoxic T-Lymphocytes
United States Food and Drug Administration
Immunosuppressive Agents
Internal Medicine
Immunotherapy
Dendritic Cells
Homeostasis
Cell Death
Lymphocytes
Pharmaceutical Preparations
Therapeutics

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Sistigu, A., Viaud, S., Chaput, N., Bracci, L., Proietti, E., & Zitvogel, L. (2011). Immunomodulatory effects of cyclophosphamide and implementations for vaccine design. Seminars in Immunopathology, 33(4), 369-383.

Immunomodulatory effects of cyclophosphamide and implementations for vaccine design. / Sistigu, Antonella; Viaud, Sophie; Chaput, Nathalie; Bracci, Laura; Proietti, Enrico; Zitvogel, Laurence.

In: Seminars in Immunopathology, Vol. 33, No. 4, 07.2011, p. 369-383.

Research output: Contribution to journalArticle

Sistigu, A, Viaud, S, Chaput, N, Bracci, L, Proietti, E & Zitvogel, L 2011, 'Immunomodulatory effects of cyclophosphamide and implementations for vaccine design.', Seminars in Immunopathology, vol. 33, no. 4, pp. 369-383.
Sistigu A, Viaud S, Chaput N, Bracci L, Proietti E, Zitvogel L. Immunomodulatory effects of cyclophosphamide and implementations for vaccine design. Seminars in Immunopathology. 2011 Jul;33(4):369-383.
Sistigu, Antonella ; Viaud, Sophie ; Chaput, Nathalie ; Bracci, Laura ; Proietti, Enrico ; Zitvogel, Laurence. / Immunomodulatory effects of cyclophosphamide and implementations for vaccine design. In: Seminars in Immunopathology. 2011 ; Vol. 33, No. 4. pp. 369-383.
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